The proposed research will (1) relate particular clinical forms of systemic lupus erythematosus (SLE) to specific autoimmune abnormalities, (2) identify autoantigens in plasma and tissue fluids which react with specific autoantibodies, (3) examine mechanisms whereby autoantibodies and autoantigens or complexes thereof induce tissue damage or alter immunological competence, and (4) devise methods for biological alteration of autoimmune reactions which might be helpful in the prevention or treatment of SLE. Clinical correlations will be achieved through a new medical record and a computerized data storage system. Autoantibodies and autoantigens will be identified and isolated through recently devised methods of plasma and cell fractionation. Mechanisms will be sought whereby autoantigens influence the immunological reactivity of one another, determine the appearance of soluble immune complexes, and condition the affinity of complexes for tissue membranes and/or immunocompetent cells. Abnormalities in immunocompetent cells will be examined by in vitro cytotoxicity testing, by histocompatibility typing, and by study of altered regulatory capacity such as suppressor T cell action. Drawing on experience in transformation of a histocompatibility immunogen to a tolerogen, means will be sought to enhance the tolerogenicity of autoantigens which might be useful in achieving a biologically specific yet harmless mode of therapy for autoimmune disease.